The long-term objective of the project is to carry out molecular genetic investigations of photoreceptor processes using electroretinogram (ERG)-defective mutants of Drosophila. Analysis of three groups of mutants (corresponding to three genes) either has just been completed or is nearing completion. One of them, TrpP365, is a novel mutation of the trp gene that causes massive degeneration of photoreceptors by a novel mechanism. The genes corresponding to the other two mutant groups encode novel proteins that are apparently important in TRP Ca2+ channel function and neurotransmission, respectively. Molecular, biochemical, cell biological, and physiological studies of these mutants and the corresponding proteins are proposed to elucidate the mechanisms of action of the two novel proteins, the nature of degeneration caused by TrpP365, and possible means of blocking this degeneration. Because the TRP protein is phylogenetically conserved, the TrpP365-caused cell degeneration is likely to be a wide-spread phenomenon. Any means of blocking this degeneration would have important ramifications. The proposed investigations of the novel proteins potentially involved in TRP function and synaptic transmission are likely to provide new insight into these processes.